Knowledge of the structural alterations in the biosynthesis of collagen is required to identify defective steps involved in connective tissue disorders. Our project is concerned with a crucial step in collagen production, namely the post-translational hydroxylation of selected proline residues by prohylhydroxylase. The proposed studies involve: (a) the synthesis of a variety of model peptides and polypeptides and study of their conformation and interaction with prolylhydroxylase, to understand the structural demands of the enzyme in its substrates, (b) the mimicking of the in vivo conformational changes in the nascent procollagen molecules during proline hydroxylation using appropriate model peptide systems and identify the ultimate conformation of these peptides, and (c) synthesis and conformational studies of several hydroxyproline-containing peptides and polypeptides to know the specific role of this unique imino acid in collagen structure. The peptides used will be of the types: (Gly-X-Pro)n, (Gly-X-Hyp)n, Gly-X-Pro(or Hyp)-Gly-X, (Gly-Hyp-X)n and (Pro-D-Ala-X)n, where X double bond Ala, Leu, Val or Sar. Studies on the interaction of these peptides with fibronectin will also be undertaken to find out the conformational features of the sites in collagen involved in its binding to fibronectin.